The candidate, Dr. Lakshmi Devi holds a Ph.D. degree from the University of Windsor, Canada and is a Professor in the Department of Pharmacology and Biological Chemistry, Mount Sinai School of Medicine. She is currently funded by two independent grants; DA 08863 from NIDA/NIH-to study post-translational regulation of opioid receptors and NS 26880 from NINDS/NIH-to study regulation of opioid peptide biosynthesis. The long-term career goals of the candidate are to explore the contribution of opioid receptor characteristics to development of drug addiction and to identify molecules and pathways involved in this process with the intent of developing pharmacological tools to help in the prevention and/or treatment of drug abuse. Mount Sinai School of Medicine provides the intellectual environment for synergistic and collaborative interactions necessary to achieve this goal. The Senior Scientist Award will facilitate this by relieving considerable amount of teaching and administrative duties. This plan has the full support of the Department of Pharmacology and Biological Chemistry and of the School. The focus of studies in Dr. Devi's laboratory has been to explore molecular mechanisms modulating opioid receptor function. The objectives of the studies proposed in this grant application are to examine novel mechanisms such as receptor dimerization that can modulate opioid receptor function and to explore the involvement of processing enzymes in the regulation of neuropeptide levels. The specific aims are: (i) to investigate heterodimerization between opioid receptor types in modulating receptor function, (ii) to explore the role of heterodimerization between opioid receptors and other GPCRsin modulating receptor function, (iii) to delineate the domains and residues of opioid receptors involved in dimerization and (iv) to explore the physiological involvement of processing enzymes in neuropeptide biosynthesis. The studies described in this grant application will provide critical information on early events that modulate opioid receptor function. Elucidation of the cellular pathways involved in modulation of receptor function is a compelling strategy for identifying appropriate pharmacological interventions for drug addiction.